Regeneration of chronic tympanic membrane perforation using an EGF-releasing chitosan patch

Most chronic tympanic membrane (TM) perforations require surgical interventions such as tympanoplasty because, unlike with acute perforations, it is very difficult for the perforations to heal spontaneously. The purpose of this study was to develop novel therapeutic techniques and scaffolds that release growth factors to treat chronic TM perforations. We evaluated the cell proliferation effects of the epidermal growth factor (EGF) and fibroblast growth factor (FGF) on in vitro cultures of TM cells using an MTT assay. They both showed similar efficacy, so we used EGF because of its lower cost. We then constructed an EGF-releasing chitosan patch scaffold (EGF-CPS) based on previous studies. We analyzed its toxicity and strength, and we studied it using scanning electron microscopy. EGF was released from the EGF-CPS for 8 weeks in an in vitro system. In animal studies, the EGF group, which was treated with EGF-CPS, showed healing in 56.5% of the animals (13/23), while the control group, which did not receive any treatment, revealed 20.8% healing (4/24) (p=0.04). Transmission electron microscopic studies of regenerated eardrums in the EGF group showed much greater preservation of histological features, and TMs of the EGF group were thinner than spontaneously healed TMs. In conclusion, this novel EGF-CPS can be used as a nonsurgical intervention technique for treatment of chronic TM perforations.